Angiotensin-converting enzyme inhibitors

Abstract

Compounds of the formula ##STR1## and their pharmaceutically acceptable salts, wherein the substituents are as defined herein, having antihypertensive activity.

We claim: 
     
       1. Compounds of the formula ##STR20## and their pharmaceutically-acceptable salts, wherein R 4  is lower alkyl or amino-lower alkyl, A and A' are independently hydroxy, lower alkoxy, or benzyloxy,   M and M' are connected together to form an alkylene bridge of from 2 to 4 carbon atoms or together with the N and C to which they are connected form a 1,2,3,4-tetrahydro-isoquinoline ring, and   Z is --(CH 2 ) 2  --, --(CH 2 ) 3  --, --(CH 2 ) 4  -- or --(CH 2 ) 5  --.   
     
     
       2. The compounds and salts according to claim 1 wherein M and M' form a 1,2,3,4-tetrahydro-isoquinoline ring. 
     
     
       3. The compound according to claim 2 which is N-(1-carboxy-1-cyclohexyl)-alanyl-(1,2,3,4-tetrahydro-3-carboxy)-isoquinoline, and pharmaceutically acceptable salts thereof. 
     
     
       4. The compound according to claim 2 which is N-(1-carbethoxy-1-cyclohexyl)-alanyl-(1,2,3,4-tetrahydro-3-carboxy)-isoquinoline, and pharmaceutically acceptable salts thereof. 
     
     
       5. The compound according to claim 2 which is N-(1-carbethoxy-1-cyclohexyl)-alanyl-(1,2,3,4-tetrahydro-3-carbomethoxy)-isoquinoline, and pharmaceutically acceptable salts thereof. 
     
     
       6. The compounds and salts according to claim 1 wherein M and M' are connected together to form an alkylene bridge containing 3 carbon atoms. 
     
     
       7. The compound according to claim 6 which is N-(1-carboxy-1-cyclopentyl)-alanyl-L-proline, and pharmaceutically acceptable salts thereof. 
     
     
       8. The compound according to claim 6 which is N-(1-carbethoxy-1-cyclopentyl)-alanyl-L-proline, and pharmaceutically acceptable salts thereof. 
     
     
       9. The compound according to claim 6 which is N-(1-carbethoxy-1-cyclopentyl)-alanyl-L-proline-t-butyl ester, and pharmaceutically acceptable salts thereof. 
     
     
       10. The compound according to claim 6 which is N-(1-carbethoxy-1-cyclohexyl)-alanyl-L-proline, and pharmaceutically acceptable salts thereof. 
     
     
       11. The compound according to claim 6 which is N-(1-carbethoxy-1-cyclohexyl)-alanyl-L-proline-t-butyl ester, and pharmaceutically acceptable salts thereof. 
     
     
       12. The compound according to claim 6 which is N-(1-carboxyl-1-cyclohexyl)-alanyl-L-proline, and pharmaceutically acceptable salts thereof. 
     
     
       13. The compound according to claim 6 which is N-(1-carbethoxy-1-cyclopropyl)-alanyl proline t-butyl ester, and pharmaceutically acceptable salts thereof. 
     
     
       14. The compound according to claim 6 which is N-(1-carbethoxy-1-cyclopropyl)-alanyl proline, and pharmaceutically acceptable salts thereof. 
     
     
       15. The compound according to claim 6 which is N-(1-carbethoxy-1-cyclopentyl)-lysinyl proline, and pharmaceutically acceptable salts thereof. 
     
     
       16. The compounds and salts of claim 9 wherein there is at least one asymmetrical carbon atom, and the substituents on each asymmetrical carbon atom are in the (S) configuration. 
     
     
       17. An antihypertensive therapeutic composition comprising, in combination with at least one nontoxic pharmaceutically-acceptable extender, an angiotensin converting enzyme inhibitory amount of at least one compound or salt of claim 1. 
     
     
       18. A method of treating angiotensin related hypertension which comprises administering to a host suffering therefrom a therapeutically-effective amount of at least one compound or salt of claim 1.